The studies proposed examine the nature, mechanisms, and consequences of the interactions of two major environmental pollutants, lead and polychlorinated biphenyls (PCBs), on the heme pathway; and on cytochrome P-450 and the mixed function oxidase system coupled to this heme-protein. Heme and P-450 play a central role in detoxification mechanisms for drugs, hormones, carcinogens and many chemically diverse substances derived from the environment. Lead and PCBs are ubiquitously distributed in the ecosystem of man; produce acute and chronic human diseases; and have potent interactions with the heme P-450 systems. These interactions are of an inhibitory nature with respect to lead; and of a stimulatory nature with respect to the PCBs. Thus, lead and PCBs serve as excellent model substances for defining in chemical terms, the biological impact of many environmental pollutants which inhibit or induce the heme-P-450 complex. Lead and PCB-induced alterations in heme synthesis and in the activities of P-450 coupled enzymes, can be expected to have major pharmacological and toxicological consequences, since the biological actions of drugs, hormones, carcinogens and other chemicals are determined to a significant degree by the rates at which they are metabolized.